CYP7A1

protein-coding

cytochrome P450 family 7 subfamily A member 1, the group of Cytochrome P450 family 7

Gene summary

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway in the liver, which converts cholesterol to bile acids. This reaction is the rate limiting step and the major site of regulation of bile acid synthesis, which is the primary mechanism for the removal of cholesterol from the body. Polymorphisms in the promoter of this gene are associated with defects in bile acid synthesis. [provided by RefSeq, Feb 2010]

Previous symbols:

CYP7

MANE transcript

NM_000780.4

Inheritance

ClinVar variants

P:1U:168B:61

Top phenotype

hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr8:58,490,178-58,500,163

External References & Databases

Ensembl (ENSG00000167910)

Transcript & Mutation Effects

hg38 • Region Span ~10.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiencySUPPORTIVE

Inheritance Pattern: SD

Disease ID:MONDO:0016203

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP7A1 variants in ClinVar

3 Conditions Cataloged

not providedTotal: 189

CYP7A1-related disorderTotal: 72

not specifiedTotal: 65

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000780.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	50 clinvar		57
missense			151 clinvar	10 clinvar	1 clinvar	162
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		5 clinvar			6
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	168	60	1	230

Highest pathogenic variant AF is 0.0000030979663

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000780.4	RefSeq	NP_000771.2	6	MANE Select
ENST00000301645.4	Ensembl	ENSP00000301645.3	6	MANE Select
ENST00001138538.1	Ensembl	ENSP00000805504.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid hormone biosynthesis - Homo sapiens (human)
Bile secretion - Homo sapiens (human)
Cholesterol metabolism - Homo sapiens (human)
Primary bile acid biosynthesis - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)

Biological Process

bile acid biosynthetic process
cholesterol catabolic process
sterol metabolic process
regulation of lipid metabolic process
cholesterol homeostasis

Molecular Function

iron ion binding
cholesterol 7-alpha-monooxygenase activity
heme binding

Cellular Component

endoplasmic reticulum membrane
organelle membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301645
Coding exons: 6
Length: 10059
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.459	292	271	1.08	0.0000148	3348
Missense (PolyPhen)		125	111.32	1.1228		1366
Synonymous	-0.0291	105	105	1.00	0.00000626	945
Loss of Function	2.13	9	19.0	0.472	0.00000100	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes a rate-limiting step in cholesterol catabolism and bile acid biosynthesis by introducing a hydrophilic moiety at position 7 of cholesterol. Important for cholesterol homeostasis. {ECO:0000269|PubMed:19965590}.;

Recessive Scores

pRec: 0.672

Intolerance Scores

LoFtool: 0.730
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.774

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium